Polymeric gene delivery of ischemia-inducible VEGF significantly attenuates infarct size and apoptosis following myocardial infarct
- Authors
- Yockman, James William; Choi, Donghoon; Whitten, Matthew G.; Chang, Chien Wen; Kastenmeier, Andrew; Erickson, Hans; Albanil, Aida; Lee, Min hyung; Kim, Sung-Wan; Bull, David A.
- Issue Date
- Jan-2009
- Publisher
- SPRINGERNATURE
- Keywords
- ischemia-inducible; polymer carrier; myocardial infarction; apoptosis; angiogenesis
- Citation
- GENE THERAPY, v.16, no.1, pp.127 - 135
- Indexed
- SCIE
SCOPUS
- Journal Title
- GENE THERAPY
- Volume
- 16
- Number
- 1
- Start Page
- 127
- End Page
- 135
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/177417
- DOI
- 10.1038/gt.2008.146
- ISSN
- 0969-7128
- Abstract
- The development of clinically beneficial myocardial gene therapy has been slowed by reliance on the use of viral carriers and non-physiologic, constitutive gene expression. To specifically address these issues, we have developed a non-viral gene carrier, water-soluble lipopolymer (WSLP), and an ischemia-inducible plasmid construct expressing vascular endothelial growth factor (VEGF), pRTP801-VEGF, to treat myocardial ischemia and infarction. Rabbits underwent ligation of the circumflex artery followed by injection of (a) an ischemia-inducible VEGF gene construct in a WSLP carrier; (b) a constitutively expressed, or unregulated, SV-VEGF gene construct in a WSLP carrier; (c) WSLP carrier alone; or (d) no injection therapy. Following 4 weeks treatment, ligation alone resulted in infarction of 48 +/- 7% of the left ventricle. With injection of WSLP carrier alone, 49 +/- 6% of the left ventricle was infarcted (P = NS). The constitutively expressed gene construct, SV-VEGF, reduced the infarct size to 32 +/- 7% of the left ventricle (P = 0.007). The ischemia-inducible gene construct, RTP801-VEGF, further reduced the infarct size to 13 +/- 4% of the left ventricle (P < 0.001). The use of a non-viral carrier to deliver an ischemia-inducible VEGF construct is effective in the treatment of acutely ischemic myocardium.
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